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Biology subjects

Varnum, S.

Publications and source records attributed to Varnum, S..

2 recordsLinked to original sources

Multiplexed quantum sensing reveals coordinated thermomagnetic regulation of mitochondria

Mitochondria are multifunctional organelles that convert the potential energy stored in nutrients and intermediary metabolites into both heat and an electrochemical proton-motive force. However, how these outputs are synchronized in cells remains an enduring question. In this work, leveraging multiplexed nanodiamond quantum sensors to monitor both changes in temperature and magnetic field fluctuations in single primary cells obtained from diverse tissues in adult mice, we identified thermomagnetic correlation profiles uncovering a regulatory feedback loop in which the cell draws upon available intracellular iron to maintain the mitochondrial electrochemical gradient. These profiles reverse in cells derived from a mouse model of Leigh syndrome and raise the intriguing possibility that primary mitochondrial diseases can be understood as disorders of thermomagnetic homeostasis.

biophysics↗

MXRA8 promotes adipose tissue whitening to drive obesity

Matrix-remodeling associated 8 (MXRA8), also known as Dual immunoglobulin domain cell adhesion molecule (DICAM), is a type 1 transmembrane protein that reportedly binds the V{beta}3 integrin1 and regulates the differentiation of osteoclasts2 and chondrocytes3, tumor growth4, T cell trafficking5, and angiogenesis6. MXRA8 is also an essential entry receptor for chikungunya virus and other related arthritogenic alphaviruses.7-9 We compared MXRA8 expression in 51 tissues in the Human Protein Atlas and found it is most highly expressed in white adipose tissue (WAT), however the function of MXRA8 in WAT is unknown. Here, we found that MXRA8 expression in WAT is increased in people with obesity and that this response is also observed in a mouse model of high fat-diet (HFD)-induced obesity. Single-nucleus RNA sequencing and high-dimensional spectral flow cytometry analyses revealed that MXRA8 is expressed predominantly by adipocyte progenitor (AP) cells and mature adipocytes. MXRA8 mutant primary adipocytes from inguinal (i)WAT exhibited increased expression of Uncoupling protein 1 (UCP1), a thermogenic protein expressed by beige and brown adipocytes that limits obesity pathogenesis.10-12 Indeed, MXRA8 mutant mice fed a HFD had preserved UCP1+ beige and brown adipocytes and were protected from HFD-induced obesity in a UCP1-dependent manner. Collectively, these findings indicate that MXRA8 promotes whitening of beige and brown adipose tissues to drive obesity pathogenesis and identify MXRA8 as a possible therapeutic target to treat obesity and associated metabolic diseases.

physiology↗